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• W2591700144 abstract "•The present ENMC workshop report summarises the current state of clinical readiness for sarcoglycanopathies.•Plan of action for the next steps. Twenty-three researchers and clinicians, from 8 countries (UK, Finland, Turkey, Spain, France, Germany, Italy and Denmark), met in Evry, France, on 15–16 November 2016 to discuss clinical trial readiness for the four autosomal recessively inherited limb-girdle muscular dystrophies (LGMDs) called sarcoglycanopathies. Sarcoglycanopathies are due to mutations in one of the four sarcoglycan (SG) genes (γ, α, β and δ for LGMD2C-F, respectively; Table 1) [1Noguchi S. McNally E.M. Ben Othmane K. et al.Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy.Science. 1995; 270: 819-822Crossref PubMed Scopus (476) Google Scholar, 2Roberds S.L. Leturcq F. Allamand V. et al.Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.Cell. 1994; 78: 625-633Abstract Full Text PDF PubMed Scopus (430) Google Scholar, 3Lim L.E. Duclos F. Broux O. et al.Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12.Nat Genet. 1995; 11: 257-265Crossref PubMed Scopus (430) Google Scholar, 4Bonnemann C.G. Modi R. Noguchi S. et al.Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex.Nat Genet. 1995; 11: 266-273Crossref PubMed Scopus (424) Google Scholar, 5Nigro V. de Sa Moreira E. Piluso G. et al.Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the delta-sarcoglycan gene.Nat Genet. 1996; 14: 195-198Crossref PubMed Scopus (386) Google Scholar]. Sarcoglycanopathies are characterized, as all LGMDs by a symmetric involvement of trunk and proximal limb muscles of pelvic and shoulder girdles. Age of onset and severity are heterogeneous, ranging from severe forms with onset in the first years of life and rapid deterioration to milder forms with later onset and slower progression. To date, no treatment is available for these rare diseases. Several groups reported promising data concerning gene transfer approaches using viral vectors expressing a normal copy of the corresponding gene in sarcoglycan deficient animal models [6Dressman D. Araishi K. Imamura M. et al.Delivery of alpha- and beta-sarcoglycan by recombinant adeno-associated virus: efficient rescue of muscle, but differential toxicity.Hum Gene Ther. 2002; 13: 1631-1646Crossref PubMed Scopus (49) Google Scholar, 7Fougerousse F. Bartoli M. Poupiot J. et al.Phenotypic correction of alpha-sarcoglycan deficiency by intra-arterial injection of a muscle-specific serotype 1 rAAV vector.Mol Ther. 2007; 15: 53-61Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 8Pacak C.A. Conlon T. Mah C.S. Byrne B.J. Relative persistence of AAV serotype 1 vector genomes in dystrophic muscle.Genet Vaccines Ther. 2008; 6: 14Crossref PubMed Scopus (18) Google Scholar, 9Pacak C.A. Walter G.A. Gaidosh G. et al.Long-term skeletal muscle protection after gene transfer in a mouse model of LGMD-2D.Mol Ther. 2007; 15: 1775-1781Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 10Rodino-Klapac L.R. Lee J.S. Mulligan R.C. Clark K.R. Mendell J.R. Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D.Neurology. 2008; 71: 240-247Crossref PubMed Scopus (47) Google Scholar, 11Cordier L. Hack A.A. Scott M.O. et al.Rescue of skeletal muscles of gamma-sarcoglycan-deficient mice with adeno-associated virus-mediated gene transfer.Mol Ther. 2000; 1: 119-129Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar, 12Goehringer C. Rutschow D. Bauer R. et al.Prevention of cardiomyopathy in delta-sarcoglycan knockout mice after systemic transfer of targeted adeno-associated viral vectors.Cardiovasc Res. 2009; 82: 404-410Crossref PubMed Scopus (55) Google Scholar, 13Li J. Dressman D. Tsao Y.P. Sakamoto A. Hoffman E.P. Xiao X. rAAV vector-mediated sarcogylcan gene transfer in a hamster model for limb girdle muscular dystrophy.Gene Ther. 1999; 6: 74-82Crossref PubMed Scopus (100) Google Scholar, 14Li J. Wang D. Qian S. Chen Z. Zhu T. Xiao X. Efficient and long-term intracardiac gene transfer in delta-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectors.Gene Ther. 2003; 10: 1807-1813Crossref PubMed Scopus (57) Google Scholar]. On the basis of these results, clinical trials were initiated with encouraging results [15Mendell J.R. Rodino-Klapac L.R. Rosales X.Q. et al.Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D.Ann Neurol. 2010; 68: 629-638Crossref PubMed Scopus (185) Google Scholar, 16Herson S. Hentati F. Rigolet A. et al.A phase I trial of adeno-associated virus serotype 1-gamma-sarcoglycan gene therapy for limb girdle muscular dystrophy type 2C.Brain. 2012; 135: 483-492Crossref PubMed Scopus (68) Google Scholar]. In addition, recent reports indicated the possibility to use drugs to restore the membrane localization of several α-SG mutants [17Soheili T. Gicquel E. Poupiot J. et al.Rescue of sarcoglycan mutations by inhibition of endoplasmic reticulum quality control is associated with minimal structural modifications.Hum Mutat. 2012; 33: 429-439Crossref PubMed Scopus (32) Google Scholar, 18Bartoli M. Gicquel E. Barrault L. et al.Mannosidase I inhibition rescues the human alpha-sarcoglycan R77C recurrent mutation.Hum Mol Genet. 2008; 17: 1214-1221Crossref PubMed Scopus (47) Google Scholar, 19Gastaldello S. D'Angelo S. Franzoso S. et al.Inhibition of proteasome activity promotes the correct localization of disease-causing alpha-sarcoglycan mutants in HEK-293 cells constitutively expressing beta-, gamma-, and delta-sarcoglycan.Am J Pathol. 2008; 173: 170-181Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 20Bianchini E. Fanin M. Mamchaoui K. Betto R. Sandona D. Unveiling the degradative route of the V247M alpha-sarcoglycan mutant responsible for LGMD-2D.Hum Mol Genet. 2014; 23: 3746-3758Crossref PubMed Scopus (26) Google Scholar]. These emerging opportunities to treat sarcoglycanopathies warrant a more in-depth understanding of their disease course. The objectives of the workshop were therefore to review the clinical phenotypes of patients with sarcoglycanopathies, to evaluate the need for natural history studies, which could point to sensitive and clinically meaningful outcome measures for follow-up and endpoints in clinical trials, to evaluate the state of patient registries and to discuss other preparatory work needed to implement clinical trials in the near future.Table 1The correspondence between the disease, the gene, its chromosomal location, the protein, its size and the references of the identification of the gene.DiseaseGeneChromosomeNameSize of the proteinReferenceLGMD2CSGCG13q12γ-Sarcoglycan35 kDa[1]Noguchi S. McNally E.M. Ben Othmane K. et al.Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy.Science. 1995; 270: 819-822Crossref PubMed Scopus (476) Google ScholarLGMD2DSGCA17q21α-Sarcoglycan50 kDa[2]Roberds S.L. Leturcq F. Allamand V. et al.Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.Cell. 1994; 78: 625-633Abstract Full Text PDF PubMed Scopus (430) Google ScholarLGMD2ESGCB4q12β-Sarcoglycan43 kDa3Lim L.E. Duclos F. Broux O. et al.Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12.Nat Genet. 1995; 11: 257-265Crossref PubMed Scopus (430) Google Scholar, 4Bonnemann C.G. Modi R. Noguchi S. et al.Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex.Nat Genet. 1995; 11: 266-273Crossref PubMed Scopus (424) Google ScholarLGMD2FSGCD5q33δ-Sarcoglycan35 kDa[5]Nigro V. de Sa Moreira E. Piluso G. et al.Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the delta-sarcoglycan gene.Nat Genet. 1996; 14: 195-198Crossref PubMed Scopus (386) Google Scholar Open table in a new tab As an introduction to the workshop, Elena Pegoraro (Italy) presented an overview of the sarcoglycanopathies. The implication of sarcoglycans in their respective diseases was demonstrated between 1994 and 1996 [1Noguchi S. McNally E.M. Ben Othmane K. et al.Mutations in the dystrophin-associated protein gamma-sarcoglycan in chromosome 13 muscular dystrophy.Science. 1995; 270: 819-822Crossref PubMed Scopus (476) Google Scholar, 2Roberds S.L. Leturcq F. Allamand V. et al.Missense mutations in the adhalin gene linked to autosomal recessive muscular dystrophy.Cell. 1994; 78: 625-633Abstract Full Text PDF PubMed Scopus (430) Google Scholar, 3Lim L.E. Duclos F. Broux O. et al.Beta-sarcoglycan: characterization and role in limb-girdle muscular dystrophy linked to 4q12.Nat Genet. 1995; 11: 257-265Crossref PubMed Scopus (430) Google Scholar, 4Bonnemann C.G. Modi R. Noguchi S. et al.Beta-sarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex.Nat Genet. 1995; 11: 266-273Crossref PubMed Scopus (424) Google Scholar, 5Nigro V. de Sa Moreira E. Piluso G. et al.Autosomal recessive limb-girdle muscular dystrophy, LGMD2F, is caused by a mutation in the delta-sarcoglycan gene.Nat Genet. 1996; 14: 195-198Crossref PubMed Scopus (386) Google Scholar]. These single-pass transmembrane glycoproteins have a molecular weight ranging from 35 to 50 kDa and contain a small intracellular domain localized at the C-terminus (for α-sarcoglycan) or N-terminus (for γ-, β- and δ-sarcoglycans), a transmembrane domain and a large extracellular domain containing N-glycosylation sites. They assemble together during their trafficking in the endoplasmic reticulum and the Golgi apparatus in a subcomplex of dystrophin-associated glycoprotein complex (DGC) [21Draviam R.A. Shand S.H. Watkins S.C. The beta-delta-core of sarcoglycan is essential for deposition at the plasma membrane.Muscle Nerve. 2006; 34: 691-701Crossref PubMed Scopus (23) Google Scholar, 22Draviam R.A. Wang B. Shand S.H. Xiao X. Watkins S.C. Alpha-sarcoglycan is recycled from the plasma membrane in the absence of sarcoglycan complex assembly.Traffic. 2006; 7: 793-810Crossref PubMed Scopus (23) Google Scholar, 23Chan Y.M. Bonnemann C.G. Lidov H.G. Kunkel L.M. Molecular organization of sarcoglycan complex in mouse myotubes in culture.J Cell Biol. 1998; 143: 2033-2044Crossref PubMed Scopus (112) Google Scholar, 24Hack A.A. Lam M.Y. Cordier L. et al.Differential requirement for individual sarcoglycans and dystrophin in the assembly and function of the dystrophin-glycoprotein complex.J Cell Sci. 2000; 113: 2535-2544PubMed Google Scholar, 25Noguchi S. Wakabayashi E. Imamura M. Yoshida M. Ozawa E. Formation of sarcoglycan complex with differentiation in cultured myocytes.Eur J Biochem. 2000; 267: 640-648Crossref PubMed Scopus (56) Google Scholar, 26Shi W. Chen Z. Schottenfeld J. Stahl R.C. Kunkel L.M. Chan Y.M. Specific assembly pathway of sarcoglycans is dependent on beta- and delta-sarcoglycan.Muscle Nerve. 2004; 29: 409-419Crossref PubMed Scopus (49) Google Scholar] (Fig. 1). The DGC plays a crucial role in maintaining the linkage between the subsarcolemmal cytoskeleton and the extracellular matrix, conferring stability to the sarcolemma and protection of muscle fibers from contraction-induced damage [27Petrof B.J. Shrager J.B. Stedman H.H. Kelly A.M. Sweeney H.L. Dystrophin protects the sarcolemma from stresses developed during muscle contraction.Proc Natl Acad Sci USA. 1993; 90: 3710-3714Crossref PubMed Scopus (1179) Google Scholar, 28Cohn R.D. Campbell K.P. Molecular basis of muscular dystrophies.Muscle Nerve. 2000; 23: 1456-1471Crossref PubMed Scopus (423) Google Scholar]. Mutations in any of the sarcoglycans prevent the complex formation, leading to a variable level of secondary deficiency of the other sarcoglycans. Sarcoglycanopathies are rare diseases but make up ~10% of all LGMDs and ~37% of childhood-onset LGMDs [[29]Fanin M. Nascimbeni A.C. Aurino S. et al.Frequency of LGMD gene mutations in Italian patients with distinct clinical phenotypes.Neurology. 2009; 72: 1432-1435Crossref PubMed Scopus (77) Google Scholar]. The estimated prevalence of all sarcoglycanopathies is around 0.56 in 100.000 [30Fanin M. Duggan D.J. Mostacciuolo M.L. et al.Genetic epidemiology of muscular dystrophies resulting from sarcoglycan gene mutations.J Med Genet. 1997; 34: 973-977Crossref PubMed Scopus (80) Google Scholar, 31Pegoraro E. Hoffman E.P. Limb-girdle muscular dystrophy overview.in: Pagon R.A. Adam M.P. Ardinger H.H. GeneReviews®. University of Washington, Seattle, Seattle (WA)2000Google Scholar]. The most common sarcoglycanopathy is LGMD2D, followed by LGMD2C, LGMD2E and then LGMD2F, which is very rare [30Fanin M. Duggan D.J. Mostacciuolo M.L. et al.Genetic epidemiology of muscular dystrophies resulting from sarcoglycan gene mutations.J Med Genet. 1997; 34: 973-977Crossref PubMed Scopus (80) Google Scholar, 31Pegoraro E. Hoffman E.P. Limb-girdle muscular dystrophy overview.in: Pagon R.A. Adam M.P. Ardinger H.H. GeneReviews®. University of Washington, Seattle, Seattle (WA)2000Google Scholar]. However, frequencies vary enormously between different geographic areas. For example, LGMD2C (mutations in SGCG gene) is the predominant form in North Africa and Roma populations with a prevalence of 0.13 per 100,000 [32Bonnemann C.G. Wong J. Ben Hamida C. Hamida M.B. Hentati F. Kunkel L.M. LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta-sarcoglycan exon 3.Neuromuscul Disord. 1998; 8: 193-197Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, 33Dalichaouche I. Sifi Y. Roudaut C. et al.gamma-Sarcoglycan and dystrophin mutation spectrum in an Algerian cohort.Muscle Nerve. 2016; https://doi.org/10.1002/mus.25443Crossref PubMed Scopus (10) Google Scholar, 34Piccolo F. Jeanpierre M. Leturcq F. et al.A founder mutation in the gamma-sarcoglycan gene of gypsies possibly predating their migration out of India.Hum Mol Genet. 1996; 5: 2019-2022Crossref PubMed Google Scholar, 35Ben Othmane K. Speer M.C. Stauffer J. et al.Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy (LGMD2C).Am J Hum Genet. 1995; 57: 732-734PubMed Google Scholar] while LGMD2F (SGCD mutations) is rare in most populations but represent about 14% of sarcoglycanopathies in Brazil [[36]Moreira E.S. Vainzof M. Suzuki O.T. Pavanello R.C. Zatz M. Passos-Bueno M.R. Genotype-phenotype correlations in 35 Brazilian families with sarcoglycanopathies including the description of three novel mutations.J Med Genet. 2003; 40: E12Crossref PubMed Scopus (43) Google Scholar]. The mainstream presentation is proximal limb muscle weakness, almost always starting in lower limbs, common calf hypertrophy, early joint contractures, and normal cognition. The frequency of respiratory insufficiency and dilated cardiomyopathy vary significantly from one study to another but usually dilated cardiomyopathy is rare in LGMD2D. A number of atypical phenotypes have also been reported such as asymptomatic hyperCKaemia (∼15%) or pseudometabolic presentation [37Mongini T. Doriguzzi C. Bosone I. Chiado-Piat L. Hoffman E.P. Palmucci L. Alpha-sarcoglycan deficiency featuring exercise intolerance and myoglobinuria.Neuropediatrics. 2002; 33: 109-111Crossref PubMed Scopus (33) Google Scholar, 38Ceravolo F. Messina S. Rodolico C. Strisciuglio P. Concolino D. Myoglobinuria as first clinical sign of a primary alpha-sarcoglycanopathy.Eur J Pediatr. 2014; 173: 239-242Crossref PubMed Scopus (19) Google Scholar, 39Tarnopolsky M. Hoffman E. Giri M. Shoffner J. Brady L. Alpha-sarcoglycanopathy presenting as exercise intolerance and rhabdomyolysis in two adults.Neuromuscul Disord. 2015; 25: 952-954Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 40Krishnaiah B. Lee J.J. Wicklund M.P. Kaur D. Young girl presenting with exercise-induced myoglobinuria.Muscle Nerve. 2016; 54: 161-164Crossref PubMed Scopus (9) Google Scholar, 41Cagliani R. Comi G.P. Tancredi L. et al.Primary beta-sarcoglycanopathy manifesting as recurrent exercise-induced myoglobinuria.Neuromuscul Disord. 2001; 11: 389-394Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar, 42Pena L. Kim K. Charrow J. Episodic myoglobinuria in a primary gamma-sarcoglycanopathy.Neuromuscul Disord. 2010; 20: 337-339Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar]. In addition to clinical clues, several laboratory findings guide the clinician to diagnosis, including elevated serum creatine kinase (CK) levels, dystrophic/myopathic changes on electromyography (EMG) and dystrophic findings on muscle biopsy with sarcoglycan deficiency on western blot. In addition, muscle magnetic resonance imaging (MRI) may show characteristic findings (see Section 5.3). A definitive diagnosis is obtained via identification of two pathogenic mutations in one of the sarcoglycan genes. Clinical severity is usually correlated with residual protein quantity. Null mutations are usually associated with absent proteins and severe DMD-like phenotype while missense mutations are associated with reduced amount of protein and milder LGMD-like phenotype [43Semplicini C. Vissing J. Dahlqvist J.R. et al.Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E.Neurology. 2015; 84: 1772-1781Crossref PubMed Scopus (41) Google Scholar, 44Magri F. Nigro V. Angelini C. et al.The Italian limb girdle muscular dystrophy registry: relative frequency, clinical features, and differential diagnosis.Muscle Nerve. 2017; 55: 55-68Crossref PubMed Scopus (59) Google Scholar]. J. Andoni Urtizberea (France) recalled the exciting saga leading to the identification of a founder mutation (T151R) in the β-sarcoglycan gene in the Amish community of Southern Indiana. The Amish are part of a sub-group of Anabaptists that fled Europe due to religious persecutions and that settled in Pennsylvania, USA, first and then in neighbouring states. A high frequency of LGMD2 patients was identified in the Amish community of Indiana in the 1960s. Clinical data were collected on various fieldwork trips and genetic studies were conducted at Genethon in Evry, France, in the early 1990s. Linkage studies clearly showed genetic heterogeneity with two distinct loci identified on chromosome 15 and on chromosome 4. Patients located in Northern Indiana turned out to have LGMD2A (calpain deficiency) while the Amish cluster situated down south (in Daviess county, South Indiana) did not. This oddity led to the subsequent identification of a founder SGCE mutation in Amish families from Southern Indiana as well as from Pennsylvania. In a second part of his talk, J. Andoni presented the genetic and clinical spectrum of sarcoglycanopathies in various parts of the world (Table 2). The number of reported families is too small to give an accurate representation of the relative distribution of the different forms but it clearly indicated that sarcoglycanopathies are present worldwide, even for the rare LGMD2F.Table 2Observations of sarcoglycan patients in India, Middle-East, Africa and Madeira. In parenthesis, number of observed cases.CountryLGMD2CLGMD2DLGMD2ELGMD2FIndiaYes (8)Yes (4)Yes (1)Yes (5)LibanYesYesIranYesPalestineYes (Δ525T)Saudi ArabiaYes (1)Yes (8)Yes (4)Yes (1)Africa (Sudan)YesMadeiraYesYes Open table in a new tab Pascal Laforêt (France) presented a retrospective series of 100 patients with sarcoglycanopathy patients from Neuromuscular Centers in Paris at Pitié-Salpêtrière, Necker, Trousseau and Raymond Poincaré university hospitals. Among these patients, there is a high proportion of LGMD2C representing 54 patients, most of which carrying the Δ525T mutation frequent in populations from North Africa, followed by 41 LGMD2D patients presenting mostly missense mutations with predominately the R77C mutation and 5 LGMD2B cases. The age of onset in nearly all cases of LGMD2C is before age 10 years while it is more variable in LGMD2D but usually before 20 years of age. Nearly 70% of LGMD2D and LGMD2C patients have lost ambulation at the time of last evaluation while the LGMD2E patients appear less severe with 60% still ambulant. There is a Duchenne-like subgroup in which 50% loose ambulation before age of 18. Besides muscle weakness, a prominent feature is contracture of the lower limbs. Cardio-respiratory involvement is less frequent than in Duchenne muscular dystrophy, but present in all forms. In particular, dilated cardiomyopathy was observed in 28% of LGMD2C, 7% of LGMD2D and 20% of LGMD2E. Nearly a third of patients needed non-invasive ventilation (24% in LGMD2C, 41% in LGMD2D and none in LGMD2E). John Vissing (Denmark) presented a cohort of 22 sarcoglycanopathy patients from his clinic (twelve LGMD2D, seven LGMD2E and three LGMD2C). They constitute 11% of the LGMD cohort followed in Copenhagen. Cardiac involvement was found to be low in LGMD2D, probably due to similarity between α- and ɛ-sarcoglycans, so that ɛ-sarcoglycan can substitute for α-sarcoglycan in the heart. In contrast, cardiac failure is much more prevalent in LGMD2C and 2E [43Semplicini C. Vissing J. Dahlqvist J.R. et al.Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E.Neurology. 2015; 84: 1772-1781Crossref PubMed Scopus (41) Google Scholar, 45Sveen M.L. Thune J.J. Kober L. Vissing J. Cardiac involvement in patients with limb-girdle muscular dystrophy type 2 and Becker muscular dystrophy.Arch Neurol. 2008; 65: 1196-1201Crossref PubMed Scopus (52) Google Scholar]. Genetic composition showed a high prevalence of the common R77C mutation in LGMD2D, which was present in all patients, and was homozygous in the majority. Likewise, the S114F mutation was present in almost all the LGMD2C patients. MRI findings showed preserved muscle structure in calf muscles, even when thigh muscles were severely affected (Fig. 2). Contractile properties are severely disrupted in Becker muscular dystrophy [[46]Lokken N. Hedermann G. Thomsen C. Vissing J. Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I.Ann Neurol. 2016; 80: 466-471Crossref PubMed Scopus (38) Google Scholar]. Since sarcoglycans are part of the DGC, deficiency of sarcoglycans could likely confer an impairment of contractility. Studies to assess this are ongoing. Jordi Diaz-Manera (Spain) reviewed the data on SG patients in Spain. There are now 5 units that are considered as highly specialized in neuromuscular disorders by the Spanish Ministry of Health (three in Barcelona, one in Valencia and one in Sevilla) whereas genetic analyses of sarcoglycan are performed at three different public centres in Barcelona, Valencia and Madrid. There is a coordinated effort among 28 hospitals to centralize information on patients affected by inherited diseases through the constitution of Spanish registries of genetic diseases. The aims of these registries are to record the maximum amount of patients, to perform clinical and basic research (identification of new genes, new biomarkers and neuroimaging patterns as well as for natural history studies) and to facilitate patient recruitment for clinical trials. Nine of these registries are devoted to neuromuscular diseases. They contain patients' informed consent and they are curated by the neurologists. The registries include demographic, clinical, follow-up and treatment data. Data quality control is ensured by repeated reviewing by a project coordinator and curator. At present, the registry for Myopathies/Muscular dystrophies holds 1595 patients of which 176 are LGMD. Among the LGMDs, 17 are LGMD2C, 14 LGMD2D and 4 LGMD2E. Claudio Semplicini (Italy) presented the proposition of an Italian nationwide study on sarcoglycanopathies. This project was built on three main foundations: i) a nation-wide Italian collaborative network, established since 2008 to characterize natural history and specific outcome measures in Duchenne muscular dystrophy (DMD) [[47]Mazzone E. Martinelli D. Berardinelli A. et al.North Star Ambulatory Assessment, 6-minute walk test and timed items in ambulant boys with Duchenne muscular dystrophy.Neuromuscul Disord. 2010; 20: 712-716Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar] that contribute to standardize evaluation protocols among centres; ii) a nation-wide Italian collaborative network for LGMD that collected a huge amount of retrospective clinical data on LGMD patients [[44]Magri F. Nigro V. Angelini C. et al.The Italian limb girdle muscular dystrophy registry: relative frequency, clinical features, and differential diagnosis.Muscle Nerve. 2017; 55: 55-68Crossref PubMed Scopus (59) Google Scholar]; and iii) a recent international observational, cross-sectional study of the natural history in LGMD2E involving patients from Padova, Paris, Copenhagen, and Naples [[43]Semplicini C. Vissing J. Dahlqvist J.R. et al.Clinical and genetic spectrum in limb-girdle muscular dystrophy type 2E.Neurology. 2015; 84: 1772-1781Crossref PubMed Scopus (41) Google Scholar]. Based on these premises, a network specifically focusing on sarcoglycanopathies was established, including twelve centres spread all over the country and representing most, if not all, referral centres for neuromuscular patients in Italy (see Acknowledgments). This project was aimed to: i) define the natural history of sarcoglycanopathies in a large group of patients; ii) study a selection of potential outcome measures for clinical trials, and iii) establish a patient registry for sarcoglycanopathies. To specifically evaluate the feasibility of this proposal during the month of June 2015, each participating centre searched its databases to identify all the potential eligible patients. A total of 172 patients with a confirmed genetic diagnosis of sarcoglycanopathy were identified (83 LGMD2D, 53 LGMD2C, 30 LGMD2E, and 6 LGMD2F). The age of patients was 33.2 ± 16 years (range 2 to 74 years) and 47% of patients were non-ambulant. Benedikt Schoser (Germany) informed that in Germany the sarcoglycan gene screening has been performed at the Institute of Human Genetics in Bochum since 2001, and has allowed identification of 46 LGMD2C, 59 LGMD2D and 29 LGMD2E patients. Nowadays almost all genetic labs in Germany perform the sarcoglycan gene sequencing. In addition, routine immunohistological screening for alterations in sarcoglycans that was performed at the Friedrich-Baur-Institute in Munich in more than 8000 muscle biopsies allowed identification of 13 patients (6 LGMD2C, 5 LGMD2D and 2 LGMD2E). Benedikt Schoser presented a genetic and clinical review of these families. All LGMD2C patients have large deletions or frameshift mutations. The onset was between 10 and 16 years, presenting first as myalgia after exercise except for one case in whom it started as eosinophilic myositis [[48]Baumeister S.K. Todorovic S. Milic-Rasic V. Dekomien G. Lochmuller H. Walter M.C. Eosinophilic myositis as presenting symptom in gamma-sarcoglycanopathy.Neuromuscul Disord. 2009; 19: 167-171Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar]. No cardiac problem was reported, but respiratory problems were present in more than half of the LGM2C cases. Calf hypertrophy was frequent. For LGMD2D, the first symptoms presented as proximal weakness with variability at the age of onset with early onset around 3–4 years of age or late onset around 16–18 years of age. Only one LGMD2D patient presented a cardiac problem and none have respiratory involvement. For the LGMD2E patients, the onset presented as hyperCKmia or hypotonia. There was no cardiac problem, but one patient died of respiratory failure. Michela Guglieri (UK) summarized the experience of the John Walton Muscular Dystrophy Research Centre (JWMDRC, Newcastle Upon Tyne, UK). The JWMDRC is the national referral centre for Limb Girdle Muscular Dystrophies in the UK and offers genetic testing for all forms of LGMD including sarcoglycanopathies. From 2006 to 2016, 35 patients have been diagnosed with sarcoglycanopathies at the JWMDRC with the following proportion of the different forms: 16 patients with LGMD2C, 5 patients with LGMD2D, 8 patients with LGMD2E and 8 patients with LGMD2F. Clinical details of 28 patients (12 LGMD2C, 6 LGMD2D, 8 LGMD2E and 2 LGMD2F) regularly followed up at the centre were available. Age of onset ranged between 3 and 10 years for LGMD2C, 3–12 years for LGMD2D, 3–32 years in LGMD2E and 4–28 years in LGMD2F. Cardiac involvement (impaired left ventricular function) was reported in LGMD2E and 2C. Respiratory impairment was noted in patients with LGMDC2C, 2D and 2E and none of the LGMD2F patients. Beril Talim (Turkey) presented an overview of the sarcoglycanopathies in her country. These diseases represent almost 15–20% of all LGMD2s with the most common forms being LGMD2C and LGMD2E. They are more common in some areas of the country (South, South East and central regions) with consanguinity and family history being common. However, the number of patients is difficult to assess due to limited numbers of neuromuscular centres and unavailability of routine genetic testing. In her institute (Hacettepe University, Dept of Pediatrics), a major pediatric neuromuscular referral center, 89 muscle biopsies with sarcoglycan deficiency have been identified in the last 15 years with 78 showing a deficiency in all sarcoglycans and 11 exclusively in γ-sarcoglycan. Overall, the age of onset is in the first decade with the first symptoms being related to proximal muscle weakness. CK is usually highly elevated (×10–150) and calf hypertrophy is often noted. 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• W2591700144 cites W1104877127 @default.
• W2591700144 cites W1494261909 @default.
• W2591700144 cites W1573786554 @default.
• W2591700144 cites W1598725059 @default.
• W2591700144 cites W1791745746 @default.
• W2591700144 cites W1830007828 @default.
• W2591700144 cites W1952000723 @default.
• W2591700144 cites W1967979864 @default.
• W2591700144 cites W1968370663 @default.
• W2591700144 cites W1968813434 @default.
• W2591700144 cites W1970173236 @default.
• W2591700144 cites W1970835934 @default.
• W2591700144 cites W1972813632 @default.
• W2591700144 cites W1973410416 @default.
• W2591700144 cites W1979485619 @default.
• W2591700144 cites W1980243949 @default.
• W2591700144 cites W1982882079 @default.
• W2591700144 cites W1984725313 @default.
• W2591700144 cites W1997946559 @default.
• W2591700144 cites W1998192085 @default.
• W2591700144 cites W1999351569 @default.
• W2591700144 cites W2000575653 @default.
• W2591700144 cites W2003027306 @default.
• W2591700144 cites W2003654592 @default.
• W2591700144 cites W2014303257 @default.
• W2591700144 cites W2016369795 @default.
• W2591700144 cites W2017043948 @default.
• W2591700144 cites W2018096072 @default.
• W2591700144 cites W2023960386 @default.
• W2591700144 cites W2029325863 @default.
• W2591700144 cites W2034180487 @default.
• W2591700144 cites W2042253896 @default.
• W2591700144 cites W2044125776 @default.
• W2591700144 cites W2044406209 @default.
• W2591700144 cites W2047015778 @default.
• W2591700144 cites W2048338867 @default.
• W2591700144 cites W2050096298 @default.
• W2591700144 cites W2054594442 @default.
• W2591700144 cites W2054795920 @default.
• W2591700144 cites W2055883057 @default.
• W2591700144 cites W2060550304 @default.
• W2591700144 cites W2061808607 @default.
• W2591700144 cites W2062006811 @default.
• W2591700144 cites W2062467557 @default.
• W2591700144 cites W2062636522 @default.
• W2591700144 cites W2065704959 @default.
• W2591700144 cites W2066619852 @default.
• W2591700144 cites W2068778247 @default.
• W2591700144 cites W2069418961 @default.
• W2591700144 cites W2076120862 @default.
• W2591700144 cites W2088152227 @default.
• W2591700144 cites W2088558095 @default.
• W2591700144 cites W2093667323 @default.
• W2591700144 cites W2094826813 @default.
• W2591700144 cites W2096362679 @default.
• W2591700144 cites W2101420246 @default.
• W2591700144 cites W2104082830 @default.
• W2591700144 cites W2104414795 @default.
• W2591700144 cites W2105100205 @default.
• W2591700144 cites W2105921617 @default.
• W2591700144 cites W2107303365 @default.
• W2591700144 cites W2107703969 @default.
• W2591700144 cites W2111712137 @default.
• W2591700144 cites W2112039060 @default.
• W2591700144 cites W2123484022 @default.
• W2591700144 cites W2132935601 @default.
• W2591700144 cites W2133824298 @default.
• W2591700144 cites W2134827380 @default.

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